Glaucomas are characterized by retinal ganglion cell death, optic nerve damage and visual field loss. Significant variability within subclasses of glaucoma is common and genetic penetrance is most often much less than 100%, suggesting that the glaucomas are a complex group of diseases in which multiple genetic loci interact to cause the disease and affect its progression. The overall goal of this proposal is to use transgenic zebrafish to model human glaucomas and ultimately identify genes that act as modifiers of an established glaucoma phenotype through the following aims: (1) Generate transgenic zebrafish to model human glaucomas: Imx1b and myocilin, two genes known to contribute to glaucoma when mutated, will be manipulated to initiate this project. (2) Analyze transgenic zebrafish models for developmental and adult glaucoma phenotypes using histological, behavioral, and physiological methods to validate glaucoma phenotype. (3) Utilize transgenic zebrafish glaucoma models in a mutagenesis screen to identify dominant enhancer or suppressor genes that interact with myocilin and Imx1b. [unreadable] [unreadable]